This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Offset analgesia is a disproportionately large decrease in pain evoked by small decreases in noxious stimulus intensity. This analgesic phenomenon may represent a centrally mediated temporal contrast enhancement mechanism. Opioid mechanisms are known to naturally occur in the body (Anderson et al., 2002, Goldstein, 1976, Basbaum and Fields, 1978). These act to diminish pain in certain bodily situations. In order to test the hypothesis that offset analgesia is partially supported by these opioid mechanisms, changes in offset analgesia will be assessed in volunteers during intravenous administration of the opioid antagonist naloxone and of the opioid agonist remifentanil. The overall objectives of this study are to systematically delineate the neurophysiological and neuropharmacological mechanisms that subserve offset analgesia.